Hussman Institute for Autism, Baltimore, MD, 21201, USA.
Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), Institute of Brain Functional Genomics, School of Life Science and the Collaborative Innovation Center for Brain Science, East China Normal University, Shanghai, 200062, People's Republic of China.
Mol Brain. 2019 May 2;12(1):40. doi: 10.1186/s13041-019-0461-4.
Results of recent genome-wide association studies (GWAS) and whole genome sequencing (WGS) highlighted type II cadherins as risk genes for autism spectrum disorders (ASD). To determine whether these cadherins may be linked to the morphogenesis of ASD-relevant brain regions, in situ hybridization (ISH) experiments were carried out to examine the mRNA expression profiles of two ASD-associated cadherins, Cdh9 and Cdh11, in the developing cerebellum. During the first postnatal week, both Cdh9 and Cdh11 were expressed at high levels in segregated sub-populations of Purkinje cells in the cerebellum, and the expression of both genes was declined as development proceeded. Developmental expression of Cdh11 was largely confined to dorsal lobules (lobules VI/VII) of the vermis as well as the lateral hemisphere area equivalent to the Crus I and Crus II areas in human brains, areas known to mediate high order cognitive functions in adults. Moreover, in lobules VI/VII of the vermis, Cdh9 and Cdh11 were expressed in a complementary pattern with the Cdh11-expressing areas flanked by Cdh9-expressing areas. Interestingly, the high level of Cdh11 expression in the central domain of lobules VI/VII was correlated with a low level of expression of the Purkinje cell marker calbindin, coinciding with a delayed maturation of Purkinje cells in the same area. These findings suggest that these two ASD-associated cadherins may exert distinct but coordinated functions to regulate the wiring of ASD-relevant circuits in the cerebellum.
最近的全基因组关联研究（GWAS）和全基因组测序（WGS）的结果强调了 II 型钙黏蛋白作为自闭症谱系障碍（ASD）的风险基因。为了确定这些钙黏蛋白是否与 ASD 相关脑区的形态发生有关，进行了原位杂交（ISH）实验，以检查两种与 ASD 相关的钙黏蛋白 Cdh9 和 Cdh11 在发育中的小脑中的 mRNA 表达谱。在出生后的第一周内，Cdh9 和 Cdh11 在小脑的浦肯野细胞的分离亚群中高表达，并且随着发育的进行，这两个基因的表达都下降了。Cdh11 的发育表达主要局限于蚓部的背侧小叶（VI/VII 叶）以及相当于人类大脑中 Crus I 和 Crus II 区的外侧半球区域，这些区域已知在成人中介导高级认知功能。此外，在蚓部的 VI/VII 叶中，Cdh9 和 Cdh11 以互补的模式表达，Cdh11 表达区域被 Cdh9 表达区域包围。有趣的是，VI/VII 叶中央区域的 Cdh11 高表达与 Purkinje 细胞标志物 calbindin 的低表达相关，与同一区域的 Purkinje 细胞成熟延迟相吻合。这些发现表明，这两种与 ASD 相关的钙黏蛋白可能发挥独特但协调的功能，以调节小脑中与 ASD 相关的电路的布线。
